The bleomycins are a family of antitumor antibiotics used for the treatment of squamous cell carcinomas and malignant lymphomas. Although clinically effective, various bleomycins have exhibited pulmonary, renal and CNS toxicities; the identification of potentially more efficacious bleomycin analogs is the long-term objective of this proposal. For the four-year period of requested support, we propose to synthesize the bleomycin group antibiotics phleomycin and tallysomycin, which are known to have altered profiles of antitumor activity in animal models. Also proposed for synthesis are bleomycin congeners and "fragments" that can help to define the structural features in bleomycin responsible for its tumor-seeking properties.